crossing96/oncoscreening huggingface dataset:
Impact of Immune and Stromal Infiltration on Outcomes Following Bladder-Sparing Trimodality Therapy for Muscle-Invasive Bladder Cancer.	BACKGROUND: Bladder-sparing trimodality therapy (TMT) is an alternative to radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC), and biomarkers to inform therapy selection are needed. OBJECTIVE: To evaluate the prognostic value of immune and stromal signatures in MIBC treated with TMT. DESIGN, SETTING, AND PARTICIPANTS: We used a clinical-grade platform to perform transcriptome-wide gene expression profiling of primary tumors from 136 MIBC patients treated with TMT at a single institution. We observed 60 overall survival events at 5yr, and median follow-up time for patients without an event was 5.0yr (interquartile range 3.1, 5.0). Expression data from another cohort of 223 MIBC patients treated with neoadjuvant chemotherapy (NAC) and RC were also analyzed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Molecular subtype, immune, and stromal signatures were evaluated for associations with disease-specific survival (DSS) and overall survival (OS) in TMT patients, and in patients treated with NAC and RC. RESULTS AND LIMITATIONS: Gene expression profiling of TMT cases identified luminal (N=40), luminal-infiltrated (N=26), basal (N=54), and claudin-low (N=16) subtypes. Signatures of T-cell activation and interferon gamma signaling were associated with improved DSS in the TMT cohort (hazard ratio 0.30 [0.14-0.65], p=0.002 for T cells), but not in the NAC and RC cohort. Conversely, a stromal signature was associated with worse DSS in the NAC and RC cohort (p=0.006), but not in the TMT cohort. This study is limited by its retrospective nature. CONCLUSIONS: Higher immune infiltration in MIBC is associated with improved DSS after TMT, whereas higher stromal infiltration is associated with shorter DSS after NAC and RC. Additional studies should be conducted to determine whether gene expression profiling can predict treatment response. PATIENT SUMMARY: We used gene expression profiling to study the association between tumor microenvironment and outcomes following bladder preservation therapy for invasive bladder cancer. We found that outcomes varied with immune and stromal signatures within the tumor. We conclude that gene expression profiling has potential to guide treatment decisions in bladder cancer.	bladder
Massage and reflexology for post-operative cancer cystectomy patients: Evaluation of a pilot service.	BACKGROUND: and purpose: Radical cystectomy is a gold standard treatment for invasive bladder cancer. However the length of the operation is long and recovery is usually slow and painful. There is growing recognition of the importance of health related quality of life among patients undergoing invasive surgical procedures. In response, a massage and reflexology service was piloted and evaluated. MATERIALS AND METHODS: One hour of massage, reflexology or a combination of both was provided twice to 38 cystectomy patients by a trained therapist in their acute post-operative phase (day one and day three). Self-reported concerns, well-being and pain were measured before and immediately after the therapy. Pain was measured once more in the early evening of each therapy day. RESULTS: Self-reported concerns and pain were significantly reduced following the intervention on both days treatments were given. Pain was measured again on the evening of each of the intervention days, and this reduction was maintained on day one but not day three. Well-being scores were also significantly improved pre to post intervention on both day one and day three. Qualitative comments highlighted that this complementary therapy service was viewed both beneficial and relaxing. There were no significant differences between the different therapies used (massage, reflexology, or a combination of the two). CONCLUSION: The findings of this pilot evaluation very tentatively support the benefits of cancer cystectomy patients receiving massage and/or reflexology in their acute postoperative recovery period. There are many limitations to this evaluation. Further research utilising a randomised control methodology alongside medical, independent markers is warranted, and currently in development.	bladder
Differential expression of S1P receptor subtypes in human bladder transitional cell carcinoma.	PURPOSE: Sphingosine 1 phosphate (S1P), S1P receptors (S1PRs) and their signaling pathways play an important role in the fate of cancer cells. The expression pattern of S1PR subtypes (S1PR1-S1PR5) may alter in cancer development stages, depending on the origin and the pathologic features of tumors. The present study aimed to examine the relationship between plasma S1P levels and the expression of S1PR subtypes in bladder tumors. METHODS/PATIENTS: These changes were evaluated in terms of the pathologic grades and stages of human bladder cancer samples. For this, tumor biopsies from 41 new bladder cancer patients as well as 26 normal-looking bladder tissues were collected and processed for immunohistochemistry (IHC) and quantitative real-time RT-PCR of S1PR subtypes. Plasma S1P level was measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: The results show that tissue S1PR1, S1PR2 and S1PR3 are over-expressed in all tumors regardless of their pathological grade (~ 3, ~ 6 and ~ 104 folds, respectively). These results were corroborated by IHC data showing accumulation of S1PR subtypes 1 and 2 in the tissues. Plasma S1P in the plasma samples from patients was in the range of control samples (Controls; 256 ± 47; patients, 270 ± 41). CONCLUSIONS: Overexpression of S1PR1, S1PR2 and S1PR3 in bladder tumor biopsies which were corroborated with the pathological grades and stages may suggest that S1PR profile in tumor biopsies is a promising marker in the diagnosis of bladder carcinoma.	bladder
Survival and metastasis in muscle-invasive bladder cancer patients who present with indeterminate pulmonary nodules before treatment.	BACKGROUND: Indeterminate pulmonary nodules (IPNs) are common during initial evaluation of bladder cancer patients. Their significance is still unknown. OBJECTIVE: Determine the significance of indeterminate pulmonary nodules, including their size and number, in muscle-invasive bladder cancer patients before definitive local therapy by surgery or chemo-radiotherapy. DESIGN: Retrospective review, single-center descriptive study. SETTINGS: A tertiary cancer center. PATIENTS AND METHODS: We performed a retrospective review of patients who underwent definitive local therapy of bladder cancer by either radical cystectomy and lymph node dissection or with chemo-radiotherapy between January 1997 and December 2015. We identified patients with baseline CT scans done during staging work-up prior to definitive treatment. Patients with proven clinical metastasis at pre.sentation were excluded, while patients who had IPNs without features suggesting metastasis were included. MAIN OUTCOME MEASURES: Disease-free survival and overall survival. SAMPLE SIZE: 168 patients. RESULTS: The median age of patients at diagnosis was 66 years; 92% were males and 56% were smokers. IPNs (3 cm or less) were present in 74 patients (44.0%). Median follow-up was 24 months. IPNs were associated with decreased disease-free survival while IPNs did not affect the overall survival (HR=1.9; 95% CI: 1.1-3.4); P=.01 and HR=1.5; 95% CI: 1.0-2.5); P=.07, respectively. In addition, nodules greater than 1 cm had reduced disease-free survival (HR=2.5; 95% CI: 1.1-5.9); P=.04. In the surgery group (n=126), the median number of lymph nodes excised was 14, with no association between lymph nodes status and the presence of IPNs (P=.08). CONCLUSION: The presence of IPNs, especially nodules greater than 1 cm had a negative effect on disease-free survival. Tailored postoperative follow-up of these patients may impact disease outcomes. LIMITATIONS: The retrospective nature, the lack of standardized preoperative imaging protocols, the lack of a central radiology review and the small number of patients. CONFLICT OF INTEREST: None.	bladder
Life quality evaluation in patients with bladder cancer: A systematic review.	OBJECTIVE: To identify scale validation studies for life quality evaluation in patients with bladder cancer. METHODS: Bibliographic search was performed on MEDLINE® via ovid, EMBASE, CENTRAL and LILACS. Subsequently, each of the articles was evaluated, identifying eligibility criteria. This information was confirmed and verified by the researchers, and in cases of missing information, the authors were contacted to complete the data. Due to the nature of the study, no statistical analysis was performed. RESULTS: From 1760 articles found, only 5were included in the qualitative analysis. Five validated questionnaires for quality of life in patients with bladder cancer (BCI, EORTC QLQ-NMIBC24, FACT-VCI, BUSS, FACT-BL). The BCI; most frequently used instrument in bladder cancer studies published to date. The FACT-VCI, instrument of application limited to unique therapeutic options within the spectrum of the disease. The EORTC QLQ-NMIBC24, widely acceptable questionnaire in the European community due to its psychometric characteristics. The BUSS evaluates the patient regardless the stage of the disease. The FACT-BL evaluates life quality in patients with non-muscle invasive bladder cancer. CONCLUSION: The use of validated instruments such as: BCI, EORTC QLQ-NMIBC24, FACT-VI, BUSS and FACT-BL which allow evaluating the impact of disease and the established therapies, is recommended.	bladder
The tumor suppressor p53 can promote collective cellular migration.	Loss of function of the tumor suppressor p53 is known to increase the rate of migration of cells transiting the narrow pores of the traditional Boyden chamber assay. Here by contrast we investigate how p53 impacts the rate of cellular migration within a 2D confluent cell layer and a 3D collagen-embedded multicellular spheroid. We use two human carcinoma cell lines, the bladder carcinoma EJ and the colorectal carcinoma HCT116. In the confluent 2-D cell layer, for both EJ and HCT cells the migratory speeds and effective diffusion coefficients for the p53 null cells were significantly smaller than in p53-expressing cells. Compared to p53 expressers, p53-null cells exhibited more organized cortical actin rings together with reduced front-rear cell polarity. Furthermore, loss of p53 caused cells to exert smaller traction forces upon their substrates, and reduced formation of cryptic lamellipodia. In the 3D multicellular spheroid, loss of p53 consistently reduced collective cellular migration into surrounding collagen matrix. As regards the role of p53 in cellular migration, extrapolation from the Boyden chamber assay to other cellular microenvironments is seen to be fraught even in terms of the sign of the effect. Together, these paradoxical results show that the effects of p53 on cellular migration are context-dependent.	bladder
An unusual case of Aβ2M amyloid deposition in bladder cancer in a non-dialysis patient.	β2-microglobulin-related (Aβ2M) amyloidosis (dialysis-associated amyloidosis) is a common complication in long-term dialysis patients. An increased concentration of β2-microgloblin (β2-m) in the serum appears to be a prerequisite for Aβ2M amyloidosis, in turn causing Aβ2M amyloid deposition predominantly in the osteoarticular tissue. There are few reports, however, of Aβ2M amyloid deposition in non-dialysis patients. We describe an atypical case of a non-dialysis patient with Aβ2M amyloid deposition in bladder cancer. A Japanese man in his 80s with no history of dialysis was admitted for transurethral resection of bladder cancer. Histopathological analysis revealed a small amount of amyloid deposition in the small-vessel wall of both the peripheral urothelial carcinoma and necrotic area. Amyloid typing by immunohistochemistry was strongly positive for anti-β2-m antibody, and β2-m was most frequently detected in laser microdissection-liquid chromatography tandem mass spectrometry. Although Aβ2M amyloidosis was expected, contrary to this, the patient's serum β2-m was only 4 mg/L, although his urine β2-m level was increased at 1340 mg/L. The unique findings observed in our patient may contribute to the elucidation of the novel pathogenesis of Aβ2M amyloid fibril formation that is distinct from conventional Aβ2M amyloidosis.	bladder
Health-related quality of life after radical cystectomy and ileal orthotopic neobladder: effect of detailed continence outcomes.	PURPOSE: To objectively quantify continence rates and to correlate continence outcomes with health-related quality of life (HRQOL) after radical cystectomy and orthotopic ileal neobladder (ONB). METHODS: Questionnaires were sent to 244 patients who underwent radical cystectomy with ONB between 2004 and 2015, and information about the current continence status was retrieved. To objectify postoperative urine loss, daytime and nocturnal pad tests were performed. Continence was defined as need of up to one safety pad. HRQOL was assessed using EORTC QLQ-C30 scoring with global health status being the primary endpoint. Statistical analysis included Fisher's test, Mann-Whitney U test, Pearson's rank correlation, and binary regression models (p < 0.05). RESULTS: 178 patients (73.0%) answered the QLQ-C30 questionnaires and were included in the study. Median follow-up was 61 months. Median daytime pad use was 1 and median daily urine loss based on pad testing was 4.0 g, leading to a daytime continence rate of 48.5%. Continence had a significant impact on postoperative HRQOL (p = 0.017). ICIQ-SF score (p = 0.001, OR = 0.805) and need for condom catheter during nighttime (p = 0.015, OR = 0.123) were independent predictors for worse HRQOL outcomes based on global health status. A history of pelvic floor muscle training was an independent predictor of increased HRQOL (p = 0.009, OR = 10.459). CONCLUSIONS: Need of condom urinals and higher ICIQ-SF scores are independent predictors for worse HRQOL outcomes. We show significant beneficial effects of pelvic floor muscle training on patients' HRQOL.	bladder
MicroRNA Dysregulation and Non-Muscle-Invasive Bladder Cancer Prognosis.	BACKGROUND: The high rate of non-muscle-invasive bladder cancer recurrence is a major challenge in patient management. miRNAs functionally regulate tumor cell proliferation and invasion, and have strong potential as biomarkers because they are robust to degradation. The objective of this project was to identify reproducible prognostic miRNAs in resected non-muscle-invasive bladder tumor tissue that are predictive of the recurrent tumor phenotype. METHODS: We utilized patients diagnosed with primary non-muscle-invasive bladder cancer in three independent cohorts for a biomarker discovery/validation approach. Baseline tumor tissue from patients with the clinically challenging, non-muscle-invasive primary low stage (Ta), high grade, and T1 tumors (tumors extending into the lamina propria) comprised the discovery cohort (n = 38). We isolated the tumor tissue RNA and assessed a panel of approximately 800 miRNAs. RESULTS: miR-26b-5p was the top-ranking prognostic tumor tissue miRNA, with a time-to-recurrence HR 0.043 for levels above versus below median, (P (adj) = 0.0003). miR-26b-5p was related to a dose-response reduction in tumor recurrence, and levels above the median were also associated with reduced time-to-progression (P (adj) = 0.02). We used two independent longitudinal cohorts that included both low-grade and high-grade Ta and T1 tumors for validation and found a consistent relationship between miR-26b-5p and recurrence and progression. CONCLUSIONS: Our results suggest that miR-26b-5p levels may be prognostic for non-muscle-invasive bladder cancer recurrence, and can feasibly be assessed in baseline tumor tissue from a wide variety of clinical settings. IMPACT: Early identification of those non-muscle-invasive bladder tumor patients with refractory phenotypes would enable individualized treatment and surveillance.	bladder
Can immunization with Bacillus Calmette-Guérin (BCG) protect against Alzheimer's disease?	"Alzheimer's disease (AD) is a neurodegenerative disorder which is the most prevalent cause of dementia in the western world. Currently, it is the most expensive disease in America, costing more than heart diseases and cancer and as the world population is getting older it is expected to become the most expensive medical disorder in the world. AD is characterized by three core pathologies: accumulation of amyloid β (Aβ) plaques, neurofibrillary tangles (NFT) and sustained inflammation. It is now believed that inflammation provides the link between Aβ and NFT. The immune system is therefore, a major player in the pathogenesis of AD. Here we propose that Bacillus Calmette-Guérin (BCG) could affect the incidence of AD. Bacillus Calmette-Guérin (BCG) is a live attenuated Mycobacterium bovis preparation first developed as a vaccine against M. tuberculosis. It has been shown to be moderately effective in preventing tuberculosis, while noted to induce modifications in inflammatory response and to regulate the immune system. Intra-vesical administration of BCG is used successfully in the past four decades to prevent recurrence of non-muscle invasive bladder cancer. In this manuscript we investigate the hypothesis that exposure to BCG decreases the prevalence of AD in elderly population and that this occurs through modulation of the immune system. Our hypothesis is based on several lines of evidence: lower prevalence of AD in countries with high BCG coverage, ability of BCG to ameliorate several conditions involving the immune system like type 1 diabetes mellitus and multiple sclerosis, animal models of AD in which BCG shows therapeutic potential and a plausible molecular mechanism which may be the basis for this hypothesis. Namely, elevated systemic levels of IL-2 (as found when BCG is given intra-vesically) that amplify Treg cells that inhibit AD associated inflammation, decreased plaque formation and restore cognitive function. To test this hypothesis one may study cognition in the large available ""natural adult population"" exposed to high dose of BCG through the bladder. Bladder cancer survivors not given BCG can serve as control group. This population can be used without adding any medical intervention."	bladder
Positive Pre-cystectomy Biopsies of the Prostatic Urethra or Bladder Neck Do Not Necessarily Preclude Orthotopic Bladder Substitution.	PURPOSE: We investigated the influence of positive pre-cystectomy biopsies of the prostatic urethra in males and the bladder neck in females on urethral recurrence, cancer specific and overall survival, and functional outcomes after orthotopic bladder substitution. MATERIALS AND METHODS: We retrospectively analyzed the records of 803 consecutive patients, including 703 males and 100 females, who underwent orthotopic bladder substitution as well as pre-cystectomy biopsy of the prostatic urethra in males and the bladder neck in females, at our institution between April 1986 and December 2017. RESULTS: Pre-cystectomy biopsies were negative in 755 of the 803 patients (94%) (group 1) and positive in 48 (6%) (group 2). Biopsies in group 2 revealed carcinoma in situ in 35 of the 48 cases (73%), pTaG1/G2 in 5 (10%) and pTaG3/pT1G3 in 8 (17%). Median followup was 64 months (IQR 21-128). At a median followup of 56 months (IQR 18-127) urethral recurrence developed in 45 of the 803 patients (5.6%), including 30 of the 755 (4%) in group 1 and 15 of the 48 (31.3%) in group 2 (p <0.001). Only 10 of the 45 patients (22%) with urethral recurrence required salvage urethrectomy while locally conservative treatment was successful in 27 (60%). Of the remaining 8 patients 6 of 45 (13%) underwent synchronous palliative chemotherapy and 2 of 45 (4%) refused treatment. Multivariate regression analysis revealed a higher risk of urethral recurrence if patients had positive pre-cystectomy biopsies (group 2 HR 6.49, 95% CI 3.33-12.62, p <0.001) or received neoadjuvant or adjuvant chemotherapy (HR 3.05, 95% CI 1.66-5.59, p <0.001). Cancer specific and overall survival as well as functional outcomes were similar in the 2 groups. CONCLUSIONS: Positive pre-cystectomy biopsies prior to orthotopic bladder substitution increased the urethral recurrence rate but did not lower cancer specific or overall survival. Most urethral recurrences were managed successfully by local treatment. Orthotopic bladder substitution is an option in highly selected patients with positive, noninvasive pre-cystectomy biopsies, provided that they undergo regular followup including urethral cytology.	bladder
One-carbon metabolism biomarkers and risk of urothelial cell carcinoma in the European prospective investigation into cancer and nutrition.	Published associations between dietary folate and bladder cancer risk are inconsistent. Biomarkers may provide more accurate measures of nutrient status. This nested case-control analysis within the European Prospective Investigation into Cancer and Nutrition (EPIC) investigated associations between pre-diagnostic serum folate, homocysteine, vitamins B6 and B12 and the risk of urothelial cell carcinomas of the bladder (UCC). A total of 824 patients with newly diagnosed UCC were matched with 824 cohort members. Serum folate, homocysteine, and vitamins B6 and B12 were measured. Odds ratios (OR) and 95% confidence intervals (CI) for total, aggressive, and non-aggressive UCC were estimated using conditional logistic regression with adjustment for smoking status, smoking duration and intensity, and other potential confounders. Additionally, statistical interaction with smoking status was assessed. A halving in serum folate concentrations was moderately associated with risk of UCC (OR: 1.18; 95% CI: 0.98-1.43), in particular aggressive UCC (OR: 1.34; 95% CI: 1.02-1.75; p-heterogeneity = 0.19). Compared to never smokers in the highest quartile of folate concentrations, this association seemed only apparent among current smokers in the lowest quartile of folate concentrations (OR: 6.26; 95% CI: 3.62-10.81, p-interaction = 0.07). Dietary folate was not associated with aggressive UCC (OR: 1.26; 95% CI: 0.81-1.95; p-heterogeneity = 0.14). No association was observed between serum homocysteine, vitamins B6 and B12 and risk of UCC. This study suggests that lower serum folate concentrations are associated with increased UCC risk, in particular aggressive UCC. Residual confounding by smoking cannot be ruled out and these findings require confirmation in future studies with multiple measurements.	bladder
Utility of robot-assisted radical cystectomy with intracorporeal urinary diversion for muscle-invasive bladder cancer.	Radical cystectomy remains the gold standard for treatment of muscle-invasive bladder cancer. Robot-assisted radical cystectomy has technical advantages over laparoscopic radical cystectomy and has emerged as an alternative to open radical cystectomy. Despite the advancements in robotic surgery, experience with total intracorporeal reconstruction of urinary diversion remains limited. Most surgeons have carried out the hybrid approach of robot-assisted radical cystectomy and extracorporeal reconstruction of urinary diversion, as intracorporeal reconstruction of urinary diversion remains technically challenging. However, intracorporeal reconstruction of urinary diversion might potentially proffer additional benefits, such as decreased fluid loss, reduction in estimated blood loss and a quicker return of bowel function. The adoption of intracorporeal ileal neobladder reconstruction has hitherto been limited to high-volume academic institutions. In the present review, we compare the totally intracorporeal robot-assisted radical cystectomy approach with open radical cystectomy and robot-assisted radical cystectomy + extracorporeal reconstruction of urinary diversion in muscle-invasive bladder cancer patients.	bladder